TEAD4 Promotes Myogenic Differentiation of Porcine Skeletal Muscle Satellite Cells.

Skeletal muscle satellite cells are indispensable for muscle growth and regeneration, and their myogenic differentiation is precisely controlled by transcription factors. As a core member of the TEAD family, TEAD4 participates in various biological processes, yet its function and regulatory mechanism in porcine skeletal muscle satellite cells (PSCs) remain largely unknown. High-purity PSCs were isolated and identified from 7-day-old Large White piglets. Combined approaches of siRNA-mediated TEAD4 knockdown, RT-qPCR, Western blotting, immunofluorescence, EdU assays, and transcriptome sequencing were applied to explore the role of TEAD4 during myogenic differentiation. TEAD4 expression was gradually upregulated during PSC differentiation and positively correlated with myogenic marker genes. Knockdown of TEAD4 did not affect PSC proliferation but significantly suppressed myogenic differentiation, as indicated by reduced expression of myogenic genes and blocked myotube formation. Transcriptomic analysis demonstrated that DEGs were highly enriched in metabolic pathways, particularly the AMPK signaling pathway. TEAD4 knockdown led to excessive upregulation of PRKAG3 and prominent induction of SLC2A4. Collectively, these results indicate that TEAD4 promotes myogenic differentiation in PSCs, likely by maintaining metabolic homeostasis. This study provides the first characterization of TEAD4 in porcine skeletal muscle satellite cells and demonstrates that it promotes myogenic differentiation.